British Journal of Anaesthesia, Vol 82, Issue 5 723-730, Copyright © 1999 by The Board of Management and Trustees of the British Journal of Anaesthesia
L. A. Davies, D. L. Hamilton, P. M. Hopkins, M. R. Boyett and S. M. Harrison
We have described the concentration-dependent inotropic effects of
halothane, isoflurane and sevoflurane on rat ventricular cells and
investigated the role of the sarcoplasmic reticulum (SR) in these inotropic
actions. Single ventricular myocytes, isolated from rat hearts, were
stimulated electrically at 1 Hz and contractions recorded optically. Cells
were exposed to a range of concentrations of halothane, isoflurane or
sevoflurane for a period of 1 min to determine the concentration-dependency
of their inotropic actions. For each anaesthetic, the peak negative
inotropic action was determined early during an exposure, and sustained
negative inotropic action was measured at steady-state just before
wash-off. In some experiments, cells were equilibrated with ryanodine 1
microgramsmol litre-1 to investigate the role of the SR in these intropic
effects. Halothane caused a concentration-dependent initial increase in
contractions (to mean 130 (SEM 28)% at 10 mmol litre-1) followed by rapid
onset of a negative inotropic effect (K0.5 0.34 mmol litre-1 for peak
effect; K0.5 0.46 mmol litre-1 for sustained effect). Exposure to
isoflurane induced a small potentiation of contractions in some cells,
followed by a concentration-dependent decrease in contraction in all cells
(K0.5 0.85 mmol litre-1 for peak effect; K0.5 1.92 mmol litre-1 for
sustained effect); contractions recovered partially during a 1-min
exposure. On wash-off, contractions were increased transiently above
control. Sevoflurane caused a large initial decrease in contraction which
then returned rapidly towards control (K0.5 0.2 mmol litre-1 for peak
effect; K0.5 2.57 mmol litre-1 for sustained effect). In common with
isoflurane, removal of sevoflurane caused a transient increase in
contractions above control. After exposure to ryanodine, the positive
inotropic effects of halothane and isoflurane did not occur, and recovery
of contractions during exposure to isoflurane and sevoflurane was abolished
as was the transient increase in contractions seen on wash-off, indicating
that these effects were mediated via the SR. Halothane had the most potent
sustained negative inotropic effect but there was little difference between
the negative inotropic effects of isoflurane and sevoflurane at clinically
relevant concentrations. At higher concentrations, sevoflurane caused a
less potent negative inotropic effect than isoflurane. The SR plays a major
role in the effects of all three anaesthetics. One possible mechanism
underlying the initial potentiation of contraction by halothane (and
isoflurane) may be sensitization of the Ca(2+)-induced Ca(2+)-release
process of the SR.
LABORATORY INVESTIGATIONS
Concentration-dependent inotropic effects of halothane, isoflurane and sevoflurane on rat ventricular myocytes
School of Biomedical Sciences, University of Leeds, Leeds LS2 9NQ, UK
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